Ultrasound Neuromodulation With Transcranial Pulse Stimulation in Alzheimer Disease: A Randomized Clinical Trial

"Participants received 6 TPS applications over 2 weeks per cycle (6 verum plus 6 sham TPS applications in total), using a modified Duolith SD1 (Storz Medical AG). ... Brain stimulation targets comprised bilateral dorsolateral prefrontal cortex and inferior frontal cortex, bilateral lateral parietal cortex extending to the Wernicke area, and precuneus cortex (eFigure 2 in Supplement 2)."

Procedures, p. 2

This describes the causal intervention (TPS) and targeted frontoparietal/precuneus sites used to modulate cognitive networks, enabling tests of causal control over brain activity and behavior relevant to consciousness studies in humans .

"Comparing the conditions with respect to changes in memory-associated brain activation from baseline (interaction condition × session), significantly higher posttreatment activation was observed in the verum condition in the precuneus, a key area of the memory network, visual areas, and in frontal regions supporting executive functions (superior and inferior frontal gyrus) (Figure 3). ... No area showed higher activation in the sham compared with the verum condition."

fMRI Outcomes, p. 7

Relative to sham, the intervention increased activation in memory and executive hubs, demonstrating that externally applied stimulation can causally upregulate network activity associated with conscious cognitive processing .

Figures

Figure 3 (p. 8) : Shows causal TPS-induced increases in task-evoked activation across memory and executive regions, supporting causal control over conscious task processing .

Figure 2 (p. 7) : Behavioral improvements after TPS (vs sham), especially in younger patients, link the causal intervention to enhanced cognitive function relevant for conscious performance .

Tables

Table (p. 6) : Table. Neuropsychological Outcomes at Each Time Point in Intention-to-Treat Analysis

"Besides main effects of condition in several cognitive networks (eTable 41 and eFigure 7 in Supplement 2), the GE analysis of resting-state fMRI data revealed a significant condition × session interaction in the dorsal attention network (P = .03). These effects specifically concerned the left frontal part of the dorsal attention network (P < .05), with increased GE compared with the respective baseline (eFigure 8 in Supplement 2)."

fMRI Outcomes, p. 7

An increase in resting-state global efficiency in a frontoparietal attention network suggests stronger large-scale integration, aligning with information-integration mechanisms proposed in consciousness research .

"Analyses for the PP sample were mostly consistent with ITT results (eTables 30-35 in Supplement 2), with one major exception. For the BDI-II, significant interactions of condition × session (P = .04; ηp2 = 0.07) and condition × session × age (P = .008; ηp2 = 0.11) emerged, with significantly lower BDI-II scores 3 months post stimulation compared with baseline in the verum condition (mean [SD] verum baseline: 7.27 [5.87]; verum 3 months post stimulation: 5.27 ...)."

fMRI Outcomes and Secondary Behavioral Outcomes, p. 8

Reduced BDI-II scores following TPS indicate modulation of negative affect, directly relevant to valence and welfare dimensions of conscious experience .

"Regarding depressive symptoms, a significant reduction in BDI-II scores was found for verum TPS in the PP sample 3 months following TPS treatment."

Discussion, p. 10

The authors interpret a sustained reduction in depressive symptoms after causal neuromodulation, supporting welfare-relevant changes in conscious state .

Tables

Table (p. 6) : Table. Neuropsychological Outcomes at Each Time Point in Intention-to-Treat Analysis